Current Status of New Anticoagulants in the Management of Venous Thromboembolism

Abstract

Venous Thromboembolism, manifested as deep venous thrombosis and pulmonary embolism, is a common problem associated with significant morbidity, mortality, and resource expenditure. Unfractionated heparin, low-molecular-weight heparin, and vitamin K antagonists are the most common treatment and prophylaxis, and have demonstrated their efficacy in a vast number of previous studies. Despite their broad use, these agents have important limitations that have led to the development of new drugs in a bid to overcome the disadvantages of the old ones without decreasing their therapeutic effect. These novel medications, some approved and others in different stages of development, include direct thrombin inhibitors like dabigatran etexilate, and direct activated factor X inhibitors like rivaroxaban. The current paper will review the characteristics, clinical trial results, and current and potential therapeutic uses of these new agents with a focus on the categories of direct thrombin inhibitors and activated factor X inhibitors.

Differential profiles of thrombin inhibitors (heparin, hirudin, bivalirudin, and dabigatran) in the thrombin generation assay and thromboelastography in vitro

“…Thrombin is thus a central regulator of hemostasis and thrombosis, and a primary target for the development of anticoagulant and antithrombotic drugs [4]. Both direct and indirect thrombin inhibitors are registered products, yet their clinical profiles with regard to pharmacokinetics, dosing regimen, bleeding liabilities, and indications are different [5,6].…”

New oral pharmacotherapeutic agents for venous thromboprophylaxis after total hip arthroplasty

“…Edoxaban is approved in Japan for VTE thromboprophylaxis in major orthopedic surgery, and is under current investigation for other indications in several countries [22][23][24][25] . Betrixaban is a fourth FⅩa inhibitor that is currently under investigation for orthopedic thromboprophylaxis [26] . It is important to note that the recommended dosage for each of the drugs varies according to the treatment indication and that the recommended dosage for orthopedic thromboprophylaxis is lower than that used for VTE treatment or stroke prophylaxis in patients with atrial fibrillation.…”

“…Inhibition of thrombin disables conversion of fibrinogen to fibrin, inhibits activation of factors Ⅴ, Ⅷ, XI (factors that further promote thrombin generation), and inhibits factor XIII that promotes clot stabilization [26][27][28] . Rivaroxaban, apixaban, and edoxaban directly inhibit both free and clot-bound FⅩa, as well as prothrombinase activity.…”

Rivaroxaban in the Treatment of Venous Thromboembolism and the Prevention of Recurrences

“…1 Anticoagulation therapy is recommended for both primary prevention and treatment of VTE. [2][3][4][5][6] Until recently, it was restricted to parenteral anticoagulants for short-term therapy and oral vitamin K antagonists (VKAs) for long-term therapy. 4 The limitations of low-molecular-weight heparin (LMWH) include the route of administration, the lack of a specific antidote, and the need for dose adjustment according to renal function.…”